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NCT Number: NCT04433910

A Clinical Trial of Convalescent Plasma Compared to Best Supportive Care for Treatment of Patients With Severe COVID-19

This is a randomized, prospective, multicenter, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.

The aim of the study is to explore the therapeutic effect of convalescent plasma transfusions on the survival and course of disease of patients with severe COVID-19. Convalescent plasma will be collected from recovered COVID-19 patients.

Patients with severe COVID-19 will be randomly assigned to two groups. Patients in the treatment group will receive covalescent plasma (250 - 325 ml) on days 1, 3 and 5. Patients in the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline, patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19.

Fifty-three patients will be included in each group. Data of each patient will be collected until discharge but nor longer than day 60.

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Hospital Ulm, Ulm, Baden-Württmberg, Germany

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About this study

This is a randomized, prospective, multicentre, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.

The primary Endpoint is a dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19 within 21 days after randomization. All criteria must be met in order to fulfil the primary endpoint.

Key secondary endpoints are time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement), the frequency and severity of adverse events and the case fatality rate on day 21, 35 and 60. Further secondary endpoints refer to the course of anti-SARS-CoV-2 antibodies in plasma donors and treated patients and the impact of donor criteria on the effectiveness of plasma units.

Patients with severe COVID-19 defined by a respiratory rate ≥ 30 breaths / minute under ambient air or the requirement of any type of ventilation support or the need for ICU treatment can be included in the trial. It is planned to enrol 106 patients. Patients will be stratified according to ventilation support and/or extracorporeal oxygenation and/or ICU treatment and will be equally asigned to two groups. The treatment group receives convalescent plasma (250 - 325 ml) on day 1, 3 and 5 and the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline (i.e. day 0), patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19. A patient switching from the control group to convalescent plasma group because of progressive COVID-19 on day 14 will be considered as failure of the primary endpoint at final evaluation of the primary endpoint on day 21.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patients with SARS-CoV-2 infection and

  • age ≥ 18 years and ≤ 75 years
  • SARS-CoV-2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap)
  • severe disease defined by at least one of the following:
  • respiratory rate ≥ 30 breaths / minute under ambient air
  • requirement of any type of ventilation support
  • needs ICU treatment
  • Written informed consent by patient or legally authorized representative

Exclusion criteria

  • Accompanying diseases other than COVID-19 with an expected survival time of less than 12 months.
  • Previous treatment with any SARS-CoV-2-convalescent plasma
  • In the opinion of the clinical team, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatment
  • Interval > 72 hours since start of ventilation support
  • Not considered eligible for extracorporeal oxygenation support (even in case of severe ARDS according to Berlin classification with Horovitz-Index < 100 mg Hg)
  • Chronic obstructive lung disease (COPD), stage 4
  • Lung fibrosis with UIP pattern in CT und severe emphysema
  • Chronic heart failure NYHA >= 3 and/or pre-existing reduction of left ventricular ejection fraction to ≤ 30%
  • Shock of any type requiring ≥ 0.5 µg/kg/min noradrenaline (or equivalent) or requiring more than two types of vasopressor medication for more than 8 hours
  • Liver cirrhosis Child C
  • Liver failure: Bilirubin > 5xULN and elevation of ALT /AST (at least one >10xULN).
  • Any history of adverse reactions to plasma proteins
  • Known deficiency of immunoglobulin A
  • Pregnancy
  • Breastfeeding women
  • Volume overload until sufficiently treated
  • Participation in another clinical trial with an investigational medicinal product

Treatment and study plan

Convalesscent Plasma

Drug

Transfusion

Primary outcomes

  1. Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19.

    Time frame: Day 21

    Dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. All criteria must be met in order to fulfil the primary endpoint.

Secondary outcomes

  1. Time to clinical improvement

    Time frame: day 0 to discharge within a 60 day period

    Time to clinical improvement (defined as days from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement) (Key secondary endpoint)

  2. Frequency and severity of adverse events by CTCAE v5.0, (Key secondary endpoint)

    Time frame: day 0 to discharge within a 60 day period

  3. Case fatality rate

    Time frame: on day 21, 35 and 60

  4. Length of hospital stay Length of hospital stay (if applicable)

    Time frame: day 0 to 60

  5. Length of stay in ICU

    Time frame: day 0 to 60

  6. Duration of ventilation support / ECMO

    Time frame: day 0 to 60

  7. Time until negative SARS-CoV-2 PCR (nasopharyngeal sample)

    Time frame: day 0 to 60

    time to first negative PCR will be assessed

  8. Predictive value of comorbidities

    Time frame: day 0 to 60

    Comorbidities will be assessed and correlated to clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)

  9. Predictive value of coagulation markers

    Time frame: day 0 to 60

    Correlation of coagulation markers (D-Dimers, prothrombin time, Partial Thromboplastin Time, ATIII, Fibrinogen) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)

  10. Predictive value of inflamation

    Time frame: day 0 to 60

    Corelation of Inflammation (laboratory testing: CRP, IL-6, Ferritin, Blood cell Count) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)

  11. Percentage of former COVID-19 patients willing to donate qualifying for plasma donation.

    Time frame: through study completion, an average of 8 months

  12. Amount of Plasma Units that could be collected for the clinical trial

    Time frame: through study completion, an average of 8 months

  13. Titer of anti-SARS-CoV-2 in transfused plasma units

    Time frame: any plasmaphereseis, through study completion, an average of 8 months

  14. Impact of donor characteristics on anti-SARS-CoV-2 humoral response

    Time frame: up to 60 days

    Anti-SARS-CoV-2-antibody titers will be correlated with age; gender; severity of COVID-19; interval between resolution of symptoms and plasmapheresis of plasma donors

  15. Course of anti-SARS-CoV-2 titer in both patient groups at different time points related to transfusion of convalescent plasma

    Time frame: up to 60 days

    Neutralizing anti-SARS-CoV-2 titers were measured by PRNT

  16. Correlation of anti-SARS-CoV-2 titer in transfused plasma units and primary and key secondary outcomes.

    Time frame: day 0 to 60

    Correlation of antibody titers with: 1. "Survival and no longer fulfilling criteria of severe COVID-19"; 2. Change in WHO ordinal scale; 3. Time to clinical improvement; 4. Length of hospital stay; 5. Length of ICU stay; 6. Length of mechanical Ventilation or ECMO support.

  17. Effect of timing of plasma transfusions

    Time frame: day 0 to 60

    Effect of timing of plasma transfusions on outcome: comparison of early treatment, i.e. day 1, 3 and 5 in convalescent plasma group vs. delayed treatment, i.e. day 15, 17, 19 in patients crossing over from control group due to progressive disease on day-14 assessment.

  18. Long term survival

    Time frame: 15 month

    Long term survival up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). And high-titer group versus low -titer group versus control.

  19. Frequency of long COVID-19

    Time frame: 15 month

    Frequency of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors).And high-titer group versus low -titer group versus control.

  20. Resolution of pneumonia and functional recovery

    Time frame: 15 month

    Resolution of pneumonia and functional recovery* in patients (CCP group compared to control group and donors). Assessment will be done by CTCAE 5.0 and structured interview. And high-titer group versus low -titer group versus control.

  21. Patient Reported Outcome: FACIT Fatigue Score

    Time frame: 15 month

    FACIT Fatigue Score: 0-53 : The higher the score, the better the quality of life Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group.

  22. Patient Reported Outcome: FACIT Dyspnea Score

    Time frame: 15 month

    FACIT Dyspnea Score 1 and 2: 0-30 : The lhigher the score the worse is the dypnea Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group.

  23. Patient Reported Outcome: EQ-5D-5L visual Scale

    Time frame: 15 month

    EQ-5D-5L visual scale: 0-100, The lower the socre, the worse is the health state Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group.

  24. Patient Reported Outcome:EQ-5D-5L cross walk

    Time frame: 15 month

    EQ-5D-5L cross walk score: 0-1.0 The lower the socre, the worse is the health state Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group.

  25. Laboratory markers: D-Dimers

    Time frame: 15 month

    D-Dimers will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group.

  26. Laboratory markers: Fibrinogen

    Time frame: 15 month

    Fibronogen will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group.

  27. Laboratory markers: CRP

    Time frame: 15 month

    CRP will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group.

  28. Laboratory markers: Ferritin

    Time frame: 15 month

    Ferritin will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group.

  29. Laboratory markers: IL-6

    Time frame: 15 month

    IL-6 will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group.

  30. Severity of long COVID-19

    Time frame: 15 month

    Severity of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). Grading according Post-COVID-19 Scale from 0 (no functional limitations) to 4 (severe functional limitations). Measures will also be compeared between high-titer group versus low -titer group versus control group.

  31. Duration of long COVID-19

    Time frame: 15 month

    Duration of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). Measures will also be compeared between high-titer group versus low -titer group versus control group.

Sponsors and collaborators

Lead sponsor

Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen

Other

Registry information

Official study title

A Randomized, Prospective, Open Label Clinical Trial on the Use of Convalescent Plasma Compared to Best Supportive Care in Patients With Severe COVID-19

Acronym: CAPSID

Important dates

Study start
2020
Primary completion
2021
Study completion
2022
First posted
Jun 16, 2020
Registry last updated
Sep 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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